tbuckley/cabot-search huggingface dataset:
Indian oncologists’ perception of the benefit of antiestrogen therapy in premenopausal women with hormone receptor positive non-metastatic breast cancer: An implementation science study.
Authors: Dr Anjali Davichan, Sissmol Davis, Dr Serene Sara John, Aditya Santoki, Aju Mathew
Journal: Journal of Clinical Oncology (2023)

e18726 Background: The findings of SOFT and the TEXT trials confirm the significant benefit of deeper estrogen deprivation via ovarian function suppression (OFS) with tamoxifen (T) or aromatase inhibitors (AI) in reducing risk of recurrence in premenopausal women with hormone receptor (HR) positive breast cancer when compared with the use of tamoxifen alone. However, the decision to treat with a less or more intensive regimen is subjective to the oncologists' perception of benefit or risk. We aimed to investigate Indian oncologists' perception of benefit of various anti-estrogen therapy options in premenopausal women with high risk of recurrence. Methods: We surveyed practicing oncologists in India who treat breast cancer using a cross-sectional survey study design. We asked participants to review a clinical vignette of a young lady who was expected to have a high risk for breast cancer recurrence. We used breast cancer free interval (BCFI) as the outcome in order to compare the results of our study with the clinical trial data from SOFT and TEXT. BCFI was defined as the first occurrence of invasive loco-regional, distant or contralateral breast cancer. Oncologists were asked to designate a number between 0-100 to represent their estimation of 5-year BCFI for women with similar characteristics if they were to receive adjuvant tamoxifen with or without OFS or aromatase inhibitor with OFS. Results: 74 oncologists completed the survey. Indian oncologists estimated the 5-year BCFI for the patient in the vignette at 75.7% with the combined use of aromatase inhibitors and OFS against 64.6% with tamoxifen alone regimen. The 5 years BCFI with the combined use of tamoxifen and OFS was estimated at 71.6% (Table 1). Conclusions: The estimated absolute benefit was much lower than what was found from the two adjuvant OFS trials. An analysis of these trials have shown that patients with high recurrence risk may have an absolute benefit of 10-15% on 5-year BCFI with the use of aromatase inhibitor and OFS compared with tamoxifen alone. The oncologists in our study underestimated the benefit of such an approach. Oncologists' underestimation of the benefit of antiestrogen therapy can have significant detrimental outcomes in the management of young women diagnosed with breast cancer. We believe that such implementation science studies will help close the gap between 'what we know' and 'what we do' as physicians. [Table: see text]
Hodgkin lymphoma mortality trends in age subgroups from 1999 to 2020 in the United States.
Authors: Tony Varughese, Jamie Koprivnikar
Journal: Journal of Clinical Oncology (2023)

e19515 Background: Hodgkin Lymphoma has a bimodal distribution with the first peak between ages 15-35 and the second peak being 55 years old and older. Advancements in treatment therapies have improved mortality such that Hodgkin Lymphoma is considered a curable disease. However, treatment outcomes in elderly patients are inferior to those of younger patients. In our study, we analyzed Hodgkin Lymphoma mortality from 1999 to 2020 in the United States. We investigated age-adjusted mortality rates and annual percent changes with a sub-group analysis. Methods: Using the CDC Wonder database, we examined mortality trends from 1999 to 2020 for Hodgkin Lymphoma in adults age 55 and older in the United States. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 people and stratified patients by sex, race/ethnicity, and census region. We computed the annual percentage change trends for the respective stratification using Joinpoint regression software. Additionally, a comparison group between ages 15 and 54 was added for the analysis. Results: In the United States, between 1999 and 2020 there were 24,898 deaths from Hodgkin Lymphoma in Adults 55 and older. The overall age adjusted mortality rate improved from 1.9 per 100,000 people to 1.4, with a respective APC of -2.06%. Our subgroup analysis by sex, race, and census region showed improvements circumferentially. Males consistently had higher rates of improvement than females. Most notably black patients had the lowest difference in AAMR from 1999 to 2020 (0.2), however, white patients and Hispanic patients respectively had higher AAMRs. The comparison group ages 15-54 had lower AAMR change from 1999 to 2020 by sex, race, and region. However, the respective AAMR for the age 15-54 group was significantly lower. Conclusions: Hodgkin Lymphoma has had significant age adjusted mortality rate improvements since 1999. Comparing adults 55 and older to patients 15-54 there is still a notable difference in AAMR. The greater magnitude of improvement in AAMR in older adults with Hodgkin Lymphoma may be related to the approval of agents such as brentuximab vedotin, which has improved tolerability as compared to bleomycin. Alleviating pulmonary toxicity with this novel agent may be more relevant in an older patient population with increased comorbidities. Further, research is needed to continue to identify more efficacious and less toxic therapies for older individuals with Hodgkin Lymphoma. [Table: see text]
The voice of the breast cancer survivor: Implementation of survivorship needs assessment in an integrated health system.
Authors: Nayha Tahir, Jenny Wei, Constanza Zamani, Heather Kurz, Nancy Goler, Claudia DeYoung, Samantha Siegel, Aida Shiraz, Christine B. Weldon, Julia R. Trosman, Niharika Dixit, Raymond Liu
Journal: Journal of Clinical Oncology (2023)

e24180 Background: The population of breast cancer survivors in the US has reached 3.8 million in 2022. In times of standardized and guideline driven oncologic treatment, individual patients continue to have multitude of unique needs that may impact their long-term survival outcomes. To address whether assessment of patient needs is feasible and leads to actionable findings, we implemented a breast cancer survivor needs assessment with standardized documentation of actions taken in the electronic medical record. Methods: An adapted NCCN evaluation tool (Coleman Tool) was used in survivorship visits to assess the feasibility of needs assessment from January 2022 to June 2022 as part of a quality improvement project. The assessment was done either electronically via secure health portal prior to the visit or in person at the time of the visit. Patient, tumor, treatment characteristics as well as needs identified, and actions taken were abstracted from the electronic medical record. Fisher’s exact test used for comparisons. Results: Patients were ethnically diverse (43% White, 39% Asian, 13% Hispanic, African American 4%), English speaking (82%), and employed (50.5%). The median time from cancer diagnosis to needs assessment was 884 days. Most of the patients had Stage 1A (38.2%), were ER (91.7%) and PR (77.8%) positive and HER2 negative (73.7%). The majority underwent lumpectomy (66.4%), had radiation therapy (67.7%) and hormonal therapy (81.6%). Only 32.3% received chemotherapy. Most patients received some form of needs assessment (202 of 217, 94.0%), with 59 (29.2%) receiving pre-appointment electronic assessments with a 42.4% response rate. Major domains of needs reported by patients and actions taken are mentioned below in the table. Both pre and at visit assessments noted a high degree of treatment and physical needs that lead to subsequent actions (p value of 1.00 and 0.04 respectively). Conclusions: An adapted NCCN Needs Assessment Tool (Coleman Tool) is a practical and feasible method of assessing breast cancer survivors’ needs. The assessment can be done pre or at visit and can lead to actions which improve survivorship care. [Table: see text]
A phase 1 study of belantamab mafodotin in combination with standard of care in newly diagnosed multiple myeloma: An interim analysis of DREAMM-9.
Authors: Saad Zafar Usmani, Michał Mielnik, Ja Min Byun, Aránzazu Alonso Alonso, Al-Ola A. Abdallah, Mamta Garg, Hang Quach, Chang-Ki Min, Wojciech Janowski, Enrique M. Ocio, Katja Weisel, Albert Oriol, Irwindeep Sandhu, Paula Rodríguez-Otero, Karthik Ramasamy, Jacqueline L. Egger, Danae Williams, Jie Ma, Morrys C. Kaisermann, Marek Hus
Journal: Journal of Clinical Oncology (2023)

8018 Background: Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells via direct cell killing and anti-myeloma immune responses. DREAMM-9 (NCT04091126) is an ongoing Phase 1, randomized, dose and schedule evaluation study. It aims to evaluate belamaf plus bortezomib, lenalidomide, and dexamethasone (VRd) in adult patients (pts) with transplant-ineligible (TI) newly diagnosed MM (NDMM) and to establish the recommended dose for future development of belamaf combination therapies in the 1 st -line setting. Herein, we report updated interim-analysis data. Methods: Belamaf dose cohorts (Co1–7) are shown in the Table. VRd was given every 3 weeks (Q3W) until cycle 8, and Rd Q4W thereafter. Following safety data from Co2–5, Co6–7 were opened in parallel (randomized 1:1) and have shorter follow-up (Table). Safety was the primary endpoint; efficacy and tolerability were secondary endpoints. Minimal residual disease (MRD) was assessed by next-generation sequencing (10 -5 ). Results: As of data cutoff (Oct 20, 2022), 93 pts were treated across Co1–7. Median age (range) was 73 (51–88) years, 55% of pts were male, and 84% were white. The most commonly reported non-ocular adverse events (AEs) across all Co were thrombocytopenia (46%), constipation (36%), diarrhea (34%), and peripheral sensory neuropathy (31%). Overall, belamaf-related Grade ≥3 AEs occurred in 35% of pts and led to belamaf dose reductions in 7% and dose delays in 63% of all treated patients. Grade ≥3 ocular AEs (keratopathy and visual acuity [KVA] scale) occurred in 53% of all pts and led to dose reductions in 12% and dose delays in 52% of overall pts. Fatal AEs occurred in 7 pts, all unrelated to study treatment. Efficacy results and ocular AEs are summarized in the Table: 100% of pts responded in Co1 (1.9 mg/kg Q3/4W) and Co3 (1.9 mg/kg Q6/8W). Median time to very good partial response or better (≥VGPR) ranged from 2.1 to 3.1 months (mo) across cohorts. Highest MRD negativity (MRD[-]) rates (≥VGPR) were seen in Co1 (83%) and Co3 (67%). Conclusions: This updated interim analysis demonstrates that belamaf plus VRd has no new safety signals and provides early and deep anti-myeloma responses in pts with TI NDMM, with high MRD[-] rates. Clinical trial information: NCT04091126 . [Table: see text]
Barriers to implementing expanded access programs in oncology: A multidisciplinary perspective.
Authors: Sherry Fu, Maishara Muquith, Erin Fenske Williams, Larry D. Anderson, Jr, Tian Zhang, Shaalan Beg
Journal: Journal of Clinical Oncology (2023)

e18632 Background: Expanded access (EA) is a pathway to make investigational drugs available to patients in need but who are unable to join a trial. Despite the rapid approval time for expanded access requests by the Food and Drug Administration, EA protocols ( &gt; 1 patient) and single-use EA have limited utilization due to barriers affecting physicians, pharmacists, and clinical research office staff. We examined factors limiting the broad implementation of EA at an NCI-designated comprehensive cancer center. Methods: Semi-structured interviews were conducted with oncologists (5), pharmacists (2), and research operations leadership (1) involved with applying for and facilitating expanded access at our institution. Interviews were transcribed verbatim and grouped into themes by 2 independent coders. Results: At our institution, recent EA requests for adult patients with cancer involved anti-viral and CAR-T therapies. Participants agreed that increased EA utilization benefits patients and potentially the institution, provided the workflow is not burdensome. Major barriers include gaps in physician knowledge of institutional processes and lack of response from drug sponsors on ability to supply drug. For EA protocols ( &gt; 1 patient), there was lack of reimbursement for time and resources, particularly for regulatory coordination and pharmacy services, which often competed with clinical trial needs. EA requests are part of standard clinical care but may require reporting patient-level data to sponsors and resources similar to a clinical trial. This contributes to unclear delineation of roles between research and clinical staff, which delays communication with the pharmacy and adverse event reporting to sponsors. Across all departments, there was a desire for a centralized office or dedicated individual to support EA processes. Conclusions: Oncology professionals recognize the benefit of EA for patients with cancer. However, utilization is limited by various challenges including lack of clearly defined roles and financial support. Suggested improvements include establishing a centralized resource at the institutional level to streamline workflows. External parties such as industry, payers and advocacy groups can also enhance EA activity through defined protocols and resources for administrative support.
Oncology provider perceptions about quality care.
Authors: Adaeze Amaefule, Amy Leader, Valerie Pracilio Csik
Journal: Journal of Clinical Oncology (2023)

e18697 Background: The Sidney Kimmel Cancer Center (SKCC), an NCI-designated cancer center, is committed to improving care delivery and quality through engagement in programs such as the Center for Medicare and Medicaid Innovation (CMMI) Oncology Care Model and the American Society of Clinical Oncology (ASCO) Oncology Medical Home. To raise awareness among providers, strategies were developed to communicate priorities. The purpose of the survey was to evaluate provider perceptions of SKCC’s quality programs, the potential for impact on patient care and the tools needed to drive behavior. Methods: A survey was emailed to approximately 80 physicians at the Sidney Kidney Cancer Center. Providers’ responses were anonymous. The survey included open-ended and ranking based questions to assess provider perceptions about quality programs and patient care. A subset of items was assigned only to providers who received a monthly scorecard containing data on their individual performance. Descriptive statistics were used to analyze the data. Results: Sixty-six physicians (77% medical oncology, 18% radiation oncology, 5% surgical oncology) responded to the survey. Almost two-thirds (62%) of respondents had more than 10 years of experience. When asked if they value access to data, 45% of respondents stated they strongly agreed, 38% agreed, and 5% either disagreed or strongly disagreed. Seventy-four percent were aware of the SKCC quality metrics. In order to better impact the quality of care, oncologists stated that they would need more data (43.9%), staff/resources (19.7%), or tools (3%). Of the 43 number of oncologists who received scorecards, 63% stated they review their results. There were mixed results about whether they felt that scorecards impacted their practice: 28% strongly agreed or agreed while 37% disagreed or strongly disagreed. Additionally. 42% of respondents strongly agreed or agreed that inclusion of quality metrics in provider incentives has increased focus on quality metrics; 19% disagreed or strongly disagreed with that statement. However, only half (54%) of respondents felt that the SKCC priority metrics would impact patient care. Conclusions: Our analysis suggests that there is room for improvement in increasing provider knowledge of quality programs and initiatives and utility of the scorecard. Oncologists need better access to data, in order to better impact the quality of care provided to patients. A reassessment will be conducted to understand how improving access to direct provider feedback from scorecards impacts perceptions. Further evaluation is needed in order to identify additional areas of growth and to improve overall provider perceptions.
Pembrolizumab vs placebo for early-stage non‒small-cell lung cancer after resection and adjuvant therapy: Subgroup analysis of patients who received adjuvant chemotherapy in the phase 3 PEARLS/KEYNOTE-091 study.
Authors: Kersti Oselin, Byoung Yong Shim, Morihito Okada, Maciej Bryl, Laura Bonanno, Guzin Demirag, Ida Colantonio, Martin Kimmich, Urska Janzic, Johan F. Vansteenkiste, Reyes Bernabe Caro, Amina Scherz, Alessandra Curioni-Fontecedro, Martin Früh, Mira Wollner, Jing Yang, Nazly Shariati, Sandrine Marreaud, Solange Peters, Mary ER O'Brien
Journal: Journal of Clinical Oncology (2023)

8520 Background: In the randomized, triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), at the second interim analysis, pembrolizumab (pembro) significantly prolonged DFS vs placebo (pbo) in the overall population of patients (pts) with completely resected stage IB–IIIA NSCLC per AJCC v7 who may or may not have received adjuvant chemotherapy (chemo; up to 4 cycles) as recommended per local guidelines (n = 1177; HR, 0.76 [95% CI, 0.63–0.91]; P = 0.0014). Here we present outcomes for those pts who received 1–4 cycles of prior adjuvant chemo, per protocol. Methods: Eligible adults had pathologically confirmed, completely resected stage IB (T ≥4 cm), II, or IIIA NSCLC (AJCC v7) of any PD-L1 expression, ECOG performance status of 0 or 1, and had not received neoadjuvant radiotherapy or chemo. Pts were randomized 1:1 to pembro 200 mg or pbo Q3W for 18 doses (~1 year); receipt of adjuvant chemo (yes vs no) was one of the stratification factors. Dual primary endpoints were DFS in the ITT and PD-L1 TPS ≥50% populations. No alpha was assigned to this subgroup analysis of pts who received adjuvant chemo for 1–4 cycles per local guidelines. Results: Of 1177 pts in the ITT population, 1010 (85.8%) received adjuvant chemo and were included in this analysis (pembro, n = 506; pbo, n = 504). Pts received a median of 17 and 18 study doses, respectively. As of data cutoff (Sep 20, 2021), 52.6% in the pembro arm vs 64.9% in the pbo arm had completed treatment. Median time from randomization to data cutoff was 37.4 mo. Median (95% CI) DFS was 58.7 mo (39.2 mo–not reached [NR]) in the pembro arm vs 34.9 mo (28.6 mo–NR) in the pbo arm (HR, 0.73 [95% CI, 0.60–0.89]). Estimated 18-mo DFS rates were 73.8% and 63.1%, respectively. In pts with PD-L1 TPS ≥50% (pembro, n = 143; pbo, n = 141), median DFS was NR in both treatment arms (HR, 0.80 [95% CI, 0.54–1.20]). Grade 3–5 adverse events (AEs) occurred in 170 pts (34.3%) in the pembro arm and 128 (25.7%) in the pbo arm (grade 5, 2.2% vs 1.0%). Immune-mediated AEs and infusion reactions occurred in 195 pts (39.3%) in the pembro arm and 69 (13.8%) in the pbo arm. Conclusions: Consistent with the ITT population, pembro substantially improved DFS vs pbo in the subgroup of pts with stage IB (T2a ≥4 cm), II, or IIIA NSCLC who received adjuvant platinum-based chemo following complete resection. Based on these results, pembro was approved for adjuvant treatment in this pt population by the US FDA. Clinical trial information: NCT02504372 .
Bemcentinib and pembrolizumab in patients with relapsed mesothelioma: MIST3, a phase IIa trial with cellular and molecular correlates of efficacy.
Authors: Matthew G Krebs, Amy Branson, Shaun Barber, Charlotte Poile, Amy King, Alastair Greystoke, Sam Moody, Luke Nolan, Molly Scotland, Liz Darlison, Amrita Bajaj, Bruno Morgan, Cassandra Brookes, Peter Wells-Jordan, Catherine Jane Richards, Anne L. Thomas, Dean Anthony Fennell
Journal: Journal of Clinical Oncology (2023)

8511 Background: AXL receptor tyrosine kinase is a key facilitator of immune escape and drug resistance, conferring a more aggressive phenotype. Targeting the PD1-PDL1 axis has demonstrated significant efficacy in patients with relapsed malignant mesothelioma (MM), however, responses are only observed in a fraction of patients. Preclinical studies suggest that dual PD1 and AXL inhibition is synergistic. We developed a multi-centre, molecularly stratified phase IIa trial to evaluate the efficacy of AXL/PD-1 inhibition with bemcentinib (Bem)/pembrolizumab (Pem) and to uncover cellular and molecular determinants of efficacy as arm 3 of the Mesothelioma Stratified Therapy umbrella trial (NCT03654833, MiST3). Methods: Patients with pleural mesothelioma were enrolled. Key inclusion factors were ECOG performance status (PS) 0-1, prior platinum-based chemotherapy (maximum of 2 prior lines allowed), evidence of disease progression with measurable disease by CT (Modified RECIST 1.1), and adequate haematological/organ function. All patients received 200mg Pem IV q3W in combination with Bem, loading dose 400mg PO for the first 3 days and then 200mg od q3w. Primary endpoint was disease control rate at 12 weeks (DCR12w). Secondary endpoints: DCR at 24 weeks (DCR24w), best objective response rate (ORR) and toxicity (NCI CTCAE 4.03). Pre-treatment fresh biopsy was required to enable multiplex immunofluorescence, whole exome and RNA transcriptome sequencing. Gut microbiome 16s RNA sequencing also was undertaken at baseline (n=21). Results: Between September 2020 and March 2022, 26 patients with MM started treatment and received at least one dose of Pem Bem. Median age was 72.5 (range, 55-85) years, 88% were male 12% were female, Histology: 88% epithelioid, 8% Biphasic, 4% Sarcomatoid, ECOG PS1 77%, &gt; 1 prior systemic therapy 35%. The median cycles of Pem Bem was 4 (IQR, 2-11). The DCR12w was 46.2% (12/26) (90% confidence limit (CI), 29.2% –63.4 %;), ORR was 15.4% (95%CI, 4.4- 34.9%; all PR)) with stable disease in 57.7% (36.9 – 76.6%); DCR24w was 38.5% (10/26) (95%CI, 20.2% – 59.4%). Adverse events (any cause): ≥ grade 3 toxicities affected 38% of pts and there were no treatment-related deaths. The most frequent adverse events recorded were fatigue in 12/26 (46%) patients and nausea in 11/26 (42%) patients. Conclusions: MiST3 met its primary endpoint and warrants further evaluation. Analysis of the cellular and molecular correlates of response are ongoing and will be presented. Clinical trial information: NCT03654833 .